Dr. Jennifer Hughes Hanks is a veterinary pathologist in the final stages of her residency training. She has a long-standing interest in the pathogenesis of infectious diseases, specifically emerging and foreign animal diseases. While Dr. Hughes Hanks has considerable training in the clinical diagnosis and behavior of a wide range of infectious diseases, her research training is limited. Her goal in the next four years is to develop the skills to become an independent researcher in the field of emerging infectious disease. This proposal describes a PhD training project which will take place in the Department of Pathobiology at the Univerisity of Missouri. The training will be supervised by Charles R. Brown, a well-established research scientist. The project will be focused on the pathogenesis of Borrelia burgdorferi, the causive agent of Lyme disease, in the mouse model. Since its discovery in the mid-1970s, Lyme disease has become the most common vector- borne infectious disease in the United States and is classified as an emerging infectious disease. While significant progress has been made in understanding the mechanisms of Lyme disease pathology, especially arthritis, little is known about the basic mechanisms of spirochete transmissibility and how it avoids immune clearance. Recent work in the mouse model has illustrated that surface lipoprotein antigens, specifically OspC, expressed by B. burgdorferi organisms are critical to the survival and dissemination of the spirochete in the mammalian host by evasion of the innate immune response. In this project, the cellular immune response will be quantified histologically during the early phase of in vivo infection by OspC-deficient spirochetes (Aim 1). The cytokine/chemokine alterations at the inoculation site of wild-type mice will be determined after challenge with OspC(-) B. burgdorferi mutants (Aim 2). Variations in survivability of OspC- deficient spirochetes will be examined in KC, CXCR2, MCP-1, and CCR2 cytokine knockout mice (Aim 3). At the completion of the project, Dr. Hughes will be better equipped to achieve her long-term career objective of aiding in national biosecurity efforts by helping to prevent the spread of emerging and foreign animal diseases.